Depletion of <small>L</small>-ascorbic acid alternating with its supplementation in the treatment of patients with acute myeloid leukemia or myelodysplastic syndromes

Park, Chan H.,Kimler, Bruce F.,Yi, Seong Yoon,Park, Se Hoon,Kim, Kihyun,Jung, Chul Won,Kim, Sun Hee,Lee, Eun Ryung,Rha, Miyong,Kim, Seonwoo,Park, Mary H.,Lee, Sook J.,Park, Hye K.,Lee, Mark H.,Yoon, S Blackwell Publishing Ltd 2009 European journal of haematology Vol.83 No.2

<P>Abstract</P><P>Purpose: </P><P><SMALL>L</SMALL>-ascorbic acid (LAA) modifies the <I>in vitro</I> growth of leukemic cells from ∼50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498).</P><P>Experimental results: </P><P>During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An <I>in vitro</I> assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients.</P><P>Results: </P><P>Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the <I>in vitro</I> assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA.</P><P>Conclusions: </P><P>The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.</P>

Doxorubicin plus Docetaxel as Neoadjuvant Treatment in Patients with Locally Advanced Carcinoma of the Breast

( Se Hoo Lee ),( Young Hyuck Im ),( Soon Il Lee ),( Jinny Park ),( Ho Young Kim ),( Jung Han Kim ),( Joon Oh Park ),( Ki Hyun Kim ),( Chul Won Jung ),( Young Suk Park ),( Won Ki Kang ),( Mark H. Lee ) 대한내과학회 2003 대한내과학회 추계학술대회 Vol.65 No.10

Spatiotemporal Evolution of the Primary Glioblastoma Genome

Kim, J.,Lee, I.H.,Cho, H.,Park, C.K.,Jung, Y.S.,Kim, Y.,Nam, S.,Kim, B.,Johnson, Mark D.,Kong, D.S.,Seol, H.,Lee, J.I.,Joo, K.,Yoon, Y.,Park, W.Y.,Lee, J.,Park, Peter J.,Nam, D.H. Cell Press 2015 CANCER CELL Vol. No.

Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.

Identification of a 12-gene Fusaric Acid Biosynthetic Gene Cluster in Fusarium Species Through Comparative and Functional Genomics.

Brown, Daren W,Lee, Seung-Ho,Kim, Lee-Han,Ryu, Jae-Gee,Lee, Soohyung,Seo, Yunhee,Kim, Young Ho,Busman, Mark,Yun, Sung-Hwan,Proctor, Robert H,Lee, Theresa APS Press 2015 Molecular plant-microbe interactions Vol.28 No.3

<P>In fungi, genes involved in biosynthesis of a secondary metabolite (SM) are often located adjacent to one another in the genome and are coordinately regulated. These SM biosynthetic gene clusters typically encode enzymes, one or more transcription factors, and a transport protein. Fusaric acid is a polyketide-derived SM produced by multiple species of the fungal genus Fusarium. This SM is of concern because it is toxic to animals and, therefore, is considered a mycotoxin and may contribute to plant pathogenesis. Preliminary descriptions of the fusaric acid (FA) biosynthetic gene (FUB) cluster have been reported in two Fusarium species, the maize pathogen F. verticillioides and the rice pathogen F. fujikuroi. The cluster consisted of five genes and did not include a transcription factor or transporter gene. Here, analysis of the FUB region in F. verticillioides, F. fujikuroi, and F. oxysporum, a plant pathogen with multiple hosts, indicates the FUB cluster consists of at least 12 genes (FUB1 to FUB12). Deletion analysis confirmed that nine FUB genes, including two Zn(II)2Cys6 transcription factor genes, are required for production of wild-type levels of FA. Comparisons of FUB cluster homologs across multiple Fusarium isolates and species revealed insertion of non-FUB genes at one or two locations in some homologs. Although the ability to produce FA contributed to the phytotoxicity of F. oxysporum culture extracts, lack of production did not affect virulence of F. oxysporum on cactus or F. verticillioides on maize seedlings. These findings provide new insights into the genetic and biochemical processes required for FA production.</P>

A baseline drift detrending technique for fast scan cyclic voltammetry

DeWaele, Mark,Oh, Yoonbae,Park, Cheonho,Kang, Yu Min,Shin, Hojin,Blaha, Charles D.,Bennet, Kevin E.,Kim, In Young,Lee, Kendall H.,Jang, Dong Pyo The Royal Society of Chemistry 2017 The Analyst Vol.142 No.22

<P>Fast scan cyclic voltammetry (FSCV) has been commonly used to measure extracellular neurotransmitter concentrations in the brain. Due to the unstable nature of the background currents inherent in FSCV measurements, analysis of FSCV data is limited to very short amounts of time using traditional background subtraction. In this paper, we propose the use of a zero-phase high pass filter (HPF) as the means to remove the background drift. Instead of the traditional method of low pass filtering across voltammograms to increase the signal to noise ratio, a HPF with a low cutoff frequency was applied to the temporal dataset at each voltage point to remove the background drift. As a result, the HPF utilizing cutoff frequencies between 0.001 Hz and 0.01 Hz could be effectively used to a set of FSCV data for removing the drifting patterns while preserving the temporal kinetics of the phasic dopamine response recorded <I>in vivo</I>. In addition, compared to a drift removal method using principal component analysis, this was found to be significantly more effective in reducing the drift (unpaired <I>t</I>-test <I>p</I> < 0.0001, <I>t</I> = 10.88) when applied to data collected from Tris buffer over 24 hours although a drift removal method using principal component analysis also showed the effective background drift reduction. The HPF was also applied to 5 hours of FSCV <I>in vivo</I> data. Electrically evoked dopamine peaks, observed in the nucleus accumbens, were clearly visible even without background subtraction. This technique provides a new, simple, and yet robust, approach to analyse FSCV data with an unstable background.</P>

Does More Information in Stock Price Load to Greater or Smaller Idiosyncratic Return Volatility?

Dong Wook Lee,Mark H. Liu 한국재무학회 2006 한국재무학회 학술대회 Vol.2006 No.10

IL10 and TNF variants and risk of non-Hodgkin lymphoma among three Asian populations

Hosgood III, H. Dean,Au, Wing-Yan,Kim, Hee Nam,Liu, Jie,Hu, Wei,Tse, Jovic,Song, Bao,Wong, Kit-fai,Lee, Je-Jung,Chanock, Stephen J.,Siu, L. P.,Purdue, Mark P.,Shin, Min-ho,Yu, Jinming,Liang, Raymond,K Springer-Verlag 2013 International journal of hematology Vol.97 No.6

<P>Genetic variation in immune-related genes, such as IL10 and TNF, have been associated with the development of non-Hodgkin lymphoma (NHL) in Caucasian populations. To test the hypothesis that IL10 and TNF polymorphisms may be associated with NHL risk in Asian populations, we genotyped 20 single nucleotide polymorphisms (SNPs) within the IL10 and TNF/LTA loci in three independent case-control studies (2635 cases and 4234 controls). IL10 rs1800871, rs1800872, and rs1800896 were genotyped in all three studies, while 5 of the remaining SNPs were genotyped in two studies, and 12 in a single study. IL10 rs1800896 was associated with B cell lymphoma [per-allele odds ratio (OR)?=?1.25, 95?% confidence interval (CI)?1.08-1.45; p trend?=?0.003], specifically diffuse large B cell lymphoma (DLBCL) (per-allele OR?=?1.29, 95?% CI?1.08-1.53; p trend?=?0.004), as well as T cell lymphoma (per-allele OR?=?1.44, 95?% CI?1.13-1.82; p trend?=?0.003). TNF rs1800629, which was genotyped in only two of our studies, was also associated with B cell lymphoma (per-allele OR?=?0.77, 95?% CI?0.64-0.91; p trend?=?0.003), specifically DLBCL (per-allele OR?=?0.69, 95?% CI?0.55-0.86; p trend?=?0.001). Our findings suggest that genetic variation in IL10 and TNF may also play a role in lymphomagenesis in Asian populations.</P>

Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi

Proctor, Robert H.,McCormick, Susan P.,Kim, Hye-Seon,Cardoza, Rosa E.,Stanley, April M.,Lindo, Laura,Kelly, Amy,Brown, Daren W.,Lee, Theresa,Vaughan, Martha M.,Alexander, Nancy J.,Busman, Mark,Guti&ea Public Library of Science 2018 PLoS pathogens Vol.14 No.4

<▼1><P>Trichothecenes are a family of terpenoid toxins produced by multiple genera of fungi, including plant and insect pathogens. Some trichothecenes produced by the fungus <I>Fusarium</I> are among the mycotoxins of greatest concern to food and feed safety because of their toxicity and frequent occurrence in cereal crops, and trichothecene production contributes to pathogenesis of some <I>Fusarium</I> species on plants. Collectively, fungi produce over 150 trichothecene analogs: i.e., molecules that share the same core structure but differ in patterns of substituents attached to the core structure. Here, we carried out genomic, phylogenetic, gene-function, and analytical chemistry studies of strains from nine fungal genera to identify genetic variation responsible for trichothecene structural diversity and to gain insight into evolutionary processes that have contributed to the variation. The results indicate that structural diversity has resulted from gain, loss, and functional changes of trichothecene biosynthetic (<I>TRI</I>) genes. The results also indicate that the presence of some substituents has arisen independently in different fungi by gain of different genes with the same function. Variation in <I>TRI</I> gene duplication and number of <I>TRI</I> loci was also observed among the fungi examined, but there was no evidence that such genetic differences have contributed to trichothecene structural variation. We also inferred ancestral states of the <I>TRI</I> cluster and trichothecene biosynthetic pathway, and proposed scenarios for changes in trichothecene structures during divergence of <I>TRI</I> cluster homologs. Together, our findings provide insight into evolutionary processes responsible for structural diversification of toxins produced by pathogenic fungi.</P></▼1><▼2><P><B>Author summary</B></P><P>Toxins produced by pathogens can contribute to infection and/or colonization of hosts. Some toxins consist of a family of metabolites with similar but distinct chemical structures. This structural variation can affect biological activity, which in turn likely contributes to adaptation to different environments, including to different hosts. Trichothecene toxins consist of over 150 structurally distinct molecules produced by certain fungi, including some plant and insect pathogens. In multiple systems that have been examined, trichothecenes contribute to pathogenesis on plants. To elucidate the evolutionary processes that have given rise to trichothecene structural variation, we conducted comparative analyses of nine fungal genera, most of which produce different trichothecene structures. Using genomic, molecular biology, phylogenetic, and analytical chemistry approaches, we obtained evidence that trichothecene structural variation has arisen primarily from gain, loss, and functional changes of trichothecene biosynthetic genes. Our results also indicate that some structural changes have arisen independently in different fungi. Our findings provide insight into genetic and biochemical changes that can occur in toxin biosynthetic pathways as fungi with the pathways adapt to different environmental conditions.</P></▼2>

A Tetra(Ethylene Glycol) Derivative of Benzothiazole Aniline Enhances Ras-Mediated Spinogenesis

Megill, Andrea,Lee, Taehee,DiBattista, Amanda Marie,Song, Jung Min,Spitzer, Matthew H.,Rubinshtein, Mark,Habib, Lila K.,Capule, Christina C.,Mayer, Michael,Turner, R. Scott,Kirkwood, Alfredo,Yang, Jer Society for Neuroscience 2013 The Journal of neuroscience Vol.33 No.22

<P>The tetra(ethylene glycol) derivative of benzothiazole aniline, BTA-EG<SUB>4</SUB>, is a novel amyloid-binding small molecule that can penetrate the blood–brain barrier and protect cells from Aβ-induced toxicity. However, the effects of Aβ-targeting molecules on other cellular processes, including those that modulate synaptic plasticity, remain unknown. We report here that BTA-EG<SUB>4</SUB> decreases Aβ levels, alters cell surface expression of amyloid precursor protein (APP), and improves memory in wild-type mice. Interestingly, the BTA-EG<SUB>4</SUB>-mediated behavioral improvement is not correlated with LTP, but with increased spinogenesis. The higher dendritic spine density reflects an increase in the number of functional synapses as determined by increased miniature EPSC (mEPSC) frequency without changes in presynaptic parameters or postsynaptic mEPSC amplitude. Additionally, BTA-EG<SUB>4</SUB> requires APP to regulate dendritic spine density through a Ras signaling-dependent mechanism. Thus, BTA-EG<SUB>4</SUB> may provide broad therapeutic benefits for improving neuronal and cognitive function, and may have implications in neurodegenerative disease therapy.</P>

Virtual Reality-Induced Cortical Reorganization and Associated Locomotor Recovery in Chronic Stroke : An Experimenter-Blind Randomized Study

You, Sung H.,Jang, Sung Ho,Kim, Yun-Hee,Hallett, Mark,Ahn, Sang Ho,Kwon, Yong-Hyun,Kim, Joong Hwi,Lee, Mi Young Ovid Technologies Wolters Kluwer -American Heart A 2005 Stroke Vol.36 No.6

<P>BACKGROUND AND PURPOSE: Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients. METHODS: Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P<0.05. RESULTS: There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (P<0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (P>0.05). Motor function was significantly improved after VR (P<0.05). CONCLUSIONS: Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR.</P>